The prevalence of substrate cross-reactivity between AHL acylases and β-lactam acylases provides a glimpse of probable links between quorum sensing and antibiotic resistance in bacteria. Both these enzyme classes belong to the N-terminal nucleophile (Ntn)-hydrolase superfamily. Penicillin V acylases alongside bile salt hydrolases constitute the cholylglycine hydrolase (CGH) group of the Ntn-hydrolase superfamily. Here we report the ability of two acylases, Slac1 and Slac2, from the marine bacterium Shewanella loihica-PV4 to hydrolyze AHLs. Three-dimensional structure of Slac1reveals the conservation of the Ntn hydrolase fold and CGH active site, making it a unique CGH exclusively active on AHLs. Slac1homologs phylogenetically cluster separate from reported CGHs and AHL acylases, thereby representing a functionally distinct sub-class of CGH that might have evolved as an adaptation to the marine environment. We hypothesize that Slac1 could provide the structural framework for understanding this subclass, and further our understanding of the evolutionary link between AHL acylases and β-lactam acylases.

AHL酰基转移酶和β-内酰胺酰基转移酶之间的底物交叉反应性盛行，为细菌群体感应和抗生素抗性之间的可能联系提供了一个可能。这两个酶类别都属于N末端亲核试剂（Ntn）-水解酶超家族。青霉素V酰基转移酶与胆汁盐水解酶一起构成了Ntn-水解酶超家族的胆固醇甘氨酸水解酶（CGH）组。在这里，我们报告了来自海洋细菌希瓦氏菌-PV4的两个酰基转移酶S1 ac1和S1 ac2水解AHL的能力。Sl ac1的三维结构揭示了Ntn水解酶折叠和CGH活性位点的保守性，使其成为仅对AHL具有活性的独特CGH。SL同源的系统同源簇与已报道的CGH和AHL酰化酶分离，从而代表了CGH的一个功能独特的亚类，可能已经适应了海洋环境。我们假设Sl ac1可以为理解该亚类提供结构框架，并进一步了解AHL酰基转移酶和β-内酰胺酰基转移酶之间的进化联系。